Central Neuroinflammation in Cerebral Ischemia: The Role of Glia

Introduction

Poststroke neuroinflammation contributes to the delayed phase of neuronal cell death in the penumbra following cerebral ischemia . Therefore antiinflammatory strategies that would seek to inhibit the direct effects of inflammation on neuronal homeostasis have been the focus of numerous neuroprotective strategies, with promising results in animal models of ischemic stroke. However, this approach has failed to translate into any measurable clinical utility, and treatment options for focal ischemic stroke remain largely limited to early reperfusion via thrombolytics or clot retrieval. One explanation for the translational failure of antiinflammatory approaches is that strategies targeting neuronal survival alone may be insufficient to result in any measurable improvement in outcome. Therefore there has been an increased interest in the roles of other cell types in the inflammatory response in the brain following thrombotic stroke. Within minutes of ischemia the cascade of regional neuroinflammatory events that occurs is mediated by the activation of local microglia and astrocytes, specialized glial cells that represent the largest proportion of cells in the mammalian brain. This chapter will discuss the critical role that microglia and astrocytes play in the induction of poststroke neuroinflammation, and their potential as targets in the next generation of therapeutic strategies for thrombotic stroke.